tbuckley/cabot-search huggingface dataset:
DeepNoise: Signal and Noise Disentanglement Based on Classifying Fluorescent Microscopy Images via Deep Learning
Authors: Sen Yang, Tao Shen, Yuqi Fang, Xiyue Wang, Jun Zhang, Wei Yang, Junzhou Huang, Xiao Han
Journal: Genomics Proteomics & Bioinformatics (2022)

The high-content image-based assay is commonly leveraged for identifying the phenotypic impact of genetic perturbations in biology field. However, a persistent issue remains unsolved during experiments: the interferential technical noises caused by systematic errors (e.g., temperature, reagent concentration, and well location) are always mixed up with the real biological signals, leading to misinterpretation of any conclusion drawn. Here, we reported a mean teacher-based deep learning model (DeepNoise) that can disentangle biological signals from the experimental noises. Specifically, we aimed to classify the phenotypic impact of 1108 different genetic perturbations screened from 125,510 fluorescent microscopy images, which were totally unrecognizable by the human eye. We validated our model by participating in the Recursion Cellular Image Classification Challenge, and DeepNoise achieved an extremely high classification score (accuracy: 99.596%), ranking the 2nd place among 866 participating groups. This promising result indicates the successful separation of biological and technical factors, which might help decrease the cost of treatment development and expedite the drug discovery process. The source code of DeepNoise is available at https://github.com/Scu-sen/Recursion-Cellular-Image-Classification-Challenge.
Mechano-responsive hydrogel for direct stem cell manufacturing to therapy
Authors: Yufeng Shou, Ling Liu, Qimin Liu, Zhicheng Le, Khang Leng Lee, Hua Li, Xianlei Li, Dion Zhanyun Koh, Yuwen Wang, Tong Ming Liu, Zheng Yang, Chwee Teck Lim, Christine Cheung, Andy Tay
Journal: Bioactive Materials (2023)

Bone marrow-derived mesenchymal stem cell (MSC) is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties. Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers, but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected
Corrigendum to “Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury.” Kidney Int. 2022;101:79–91
Authors: Yu Pan, Shirong Cao, Andrew S. Terker, Jiaqi Tang, Kensuke Sasaki, Yinqiu Wang, Aolei Niu, Wentian Luo, Dhouha Daasi, Xiaofeng Fan, Suwan Wang, Matthew H. Wilson, Ming-Zhi Zhang, Raymond C. Harris
Journal: Kidney International (2023)
Hypokalemia due to ectopic adrenocorticotropic hormone secondary to metastatic lung carcinoma
Authors: Nikita Pawar, Vaibhav Tiwari, Anurag Gupta, Vinant Bhargava, Shiv Chadha, Salil Bhargava, Manish Malik, Ashwani Gupta, Anil Kumar Bhalla, D.S. Rana
Journal: Kidney International (2023)
Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial
Authors: Inez Trouwborst, Anouk Gijbels, Kelly M. Jardon, Els Siebelink, Gabby B. Hul, Lisa Wanders, Balázs Erdos, Szabolcs Péter, Cécile M. Singh-Povel, Johan de Vogel-van den Bosch, Michiel E. Adriaens, Ilja C.W. Arts, Dick H.J. Thijssen, Edith J.M. Feskens, Gijs H. Goossens, Lydia A. Afman, Ellen E. Blaak
Journal: Cell Metabolism (2023)

Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health. Women and men with MIR or LIR (n = 242, body mass index [BMI] 25–40 kg/m2, 40–75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA). PhenoDiet group B showed no significant improvements in the primary outcome disposition index, but greater improvements in insulin sensitivity, glucose homeostasis, serum triacylglycerol, and C-reactive protein compared with PhenoDiet group A were observed. We demonstrate that modulating macronutrient composition within the dietary guidelines based on tissue-specific insulin resistance (IR) phenotype enhances cardiometabolic health improvements. Clinicaltrials.gov registration: NCT03708419, CCMO registration NL63768.068.17.
Characterization difference of typical KL1, KL2 and ST11-KL64 hypervirulent and carbapenem-resistant Klebsiella pneumoniae
Authors: Ying Zhou, Chunyang Wu, Bingjie Wang, YanLei Xu, Huilin Zhao, Yinjuan Guo, Xiaocui Wu, Jingyi Yu, Lulin Rao, Xinyi Wang, Fangyou Yu
Journal: Drug Resistance Updates (2023)
Re: Andrea Loehr, Arif Hussain, Akash Patnaik, et al. Emergence of BRCA Reversion Mutations in Patients with Metastatic Castration-resistant Prostate Cancer After Treatment with Rucaparib. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.09.010
Authors: Feng Qi, Zicheng Xu, Qing Zou
Journal: European Urology (2023)
CRISPR screening reveals gleason score and castration resistance related oncodriver ring finger protein 19 A (RNF19A) in prostate cancer
Authors: Ning Zhang, Da Huang, Xiaohao Ruan, Ada Tsui-Lin Ng, James Hok-Leung Tsu, Guangliang Jiang, Jingyi Huang, Yongle Zhan, Rong Na
Journal: Drug Resistance Updates (2023)

Prostate cancer (PCa) is one of the most lethal causes of cancer-related death in male. It is characterized by chromosomal instability and disturbed signaling transduction. E3 ubiquitin ligases are well-recognized as mediators leading to genomic alterations and malignant phenotypes. There is a lack of systematic study on novel oncodrivers with genomic and clinical significance in PCa. In this study we used clustered regularly interspaced short palindromic repeats (CRISPR) system to screen 656 E3 ubiquitin ligases as oncodrivers or tumor repressors in PCa cells. We identified 51 significantly changed genes, and conducted genomic and clinical analysis on these genes. It was found that the Ring Finger Protein 19 A (RNF19A) was a novel oncodriver in PCa. RNF19A was frequently amplified and highly expressed in PCa and other cancer types. Clinically, higher RNF19A expression correlated with advanced Gleason Score and predicted castration resistance. Mechanistically, transcriptomics, quantitative and ubiquitination proteomic analysis showed that RNF19A ubiquitylated Thyroid Hormone Receptor Interactor 13 (TRIP13) and was transcriptionally activated by androgen receptor (AR) and Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A). This study uncovers the genomic and clinical significance of a oncodriver RNF19A in PCa. The results of this study indicate that targeting AR/HIF1A-RNF19A-TRIP13 signaling axis could be an alternative option for PCa diagnosis and therapy.
Cleavable collagenase-assistant nanosonosensitizer for tumor penetration and sonodynamic therapy
Authors: Ting Yin, Huaqing Chen, Aiqing Ma, Hong Pan, Ze Chen, Xiaofan Tang, Guojun Huang, Jianhong Liao, Baozhen Zhang, Mingbin Zheng, Lintao Cai
Journal: Biomaterials (2022)
An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug
Authors: Imran Ozer, Anna Slezak, Parul Sirohi, Xinghai Li, Nikita Zakharov, Yunxin Yao, Jeffrey I. Everitt, Ivan Spasojevic, Stephen L. Craig, Joel H. Collier, Jonathan E. Campbell, David A. D'Alessio, Ashutosh Chilkoti
Journal: Biomaterials (2023)
Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
Authors: Thomas F. Martinez, Sally Lyons-Abbott, Angie L. Bookout, Eduardo V. De Souza, Cynthia Donaldson, Joan M. Vaughan, Calvin Lau, Ariel Abramov, Arian F. Baquero, Karalee Baquero, Dave Friedrich, Justin Huard, Ray Davis, Bong Kim, Ty Koch, Aaron J. Mercer, Ayesha Misquith, Sara A. Murray, Sakara Perry, Lindsay K. Pino, Christina Sanford, Alex Simon, Yu Zhang, Garrett Zipp, Cristiano V. Bizarro, Maxim N. Shokhirev, Andrew J. Whittle, Brian C. Searle, Michael J. MacCoss, Alan Saghatelian, Christopher A. Barnes
Journal: Cell Metabolism (2023)

Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals
Authors: Shaunak Deota, Terry Lin, Amandine Chaix, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, Ling Huang, Satchidananda Panda
Journal: Cell Metabolism (2023)

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of feeding and fasting. In both animals and humans, TRF has pleiotropic health benefits that arise from multiple organ systems, yet the molecular basis of TRF-mediated benefits is not well understood. Here, we subjected mice to isocaloric ad libitum feeding (ALF) or TRF of a western diet and examined gene expression changes in samples taken from 22 organs and brain regions collected every 2 h over a 24-h period. We discovered that TRF profoundly impacts gene expression. Nearly 80% of all genes show differential expression or rhythmicity under TRF in at least one tissue. Functional annotation of these changes revealed tissue- and pathway-specific impacts of TRF. These findings and resources provide a critical foundation for future mechanistic studies and will help to guide human time-restricted eating (TRE) interventions to treat various disease conditions with or without pharmacotherapies.
Table of Contents
Authors: Manfred Hecking, Magdalena Madero, Friedrich Port, Daniel Schneditz, Peter Wabel, Charles Chazot, Olivier Devuyst, Krzysztof Kiryluk, Marina De Cos, Kirk Campbell, Nina Pilat, Je Ko, Jong Park, Julie Ingelfinger, Edouard Fu, Alexander Kutz, Rishi Desai, James Sharman, Markus Van Der Giet, Jürgen Floege, Pranav Garimella, Clea Du Toit, Ngoc Le, Sandosh Padmanabhan, Juan Carrero, Søren Vestergaard, Simon Kok Jensen, Alessandro Gasparini, Viyaasan Mahalingasivam, Samira Bell, Henrik Birn, Uffe Heide-Jørgensen, Catherine Clase, Faye Cleary, Josef Coresh, Friedo Dekker, Ron Gansevoort, Brenda Hemmelgarn, Kitty Jager, Tazeen Jafar, Csaba Kovesdy, Manish Sood, Bénédicte Stengel, Christian Christiansen, Dorothea Nitsch, Steicy Sobrino, Chrystelle Abdo, Bénédicte Neven, Adeline Denis, Nathalie Gouge-Biebuyck, Emmanuel Clave, Soëli Charbonnier, Tifanie Blein, Camille Kergaravat, Marion Alcantara, Patrick Villarese, Romain Berthaud, Laurène Dehoux, Souha Albinni, Esma Karkeni, Chantal Lagresle-Peyrou, Marina Cavazzana, Rémi Salomon, Isabelle André, Antoine Toubert, Vahid Asnafi, Capucine Picard, Stéphane Blanche, Elizabeth Macintyre, Olivia Boyer, Emmanuelle Six, Julien Zuber, Mark Corkins, Maryanne Achieng, Bridget Delay, Vanja Krneta-Stankic, Margo Cain, Brandy Walker, Jichao Chen, Nils Lindström, Rachel Miller
Journal: Kidney International (2023)
Immunoediting instructs tumor metabolic reprogramming to support immune evasion
Authors: Chin-Hsien Tsai, Yu-Ming Chuang, Xiaoyun Li, Yi-Ru Yu, Sheue-Fen Tzeng, Shao Thing Teoh, Katherine E. Lindblad, Mario Di Matteo, Wan-Chen Cheng, Pei-Chun Hsueh, Kung-Chi Kao, Hana Imrichova, Likun Duan, Hector Gallart-Ayala, Pei-Wen Hsiao, Massimiliano Mazzone, Julijana Ivanesevic, Xiaojing Liu, Karin E. de Visser, Amaia Lujambio, Sophia Y. Lunt, Susan M. Kaech, Ping-Chih Ho
Journal: Cell Metabolism (2023)
Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy
Authors: Ka Hong Wong, Zhaopei Guo, Di Jiang, Xingzhi Zhou, Lizhu Lin, Denggao Zhao, Meiwan Chen
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
Application of the mineral-binding protein fetuin-A for the detection of calcified lesions
Authors: Robert Dzhanaev, Christian Hasberg, Andrea Gorgels, Carlo Schmitz, Camilla Franziska Winkler, Hanna Malyaran, Steffen Gräber, Anouk Gentier, Armand Jaminon, Stijn Agten, Tilman Hackeng, Asim Cengiz Akbulut, Leon Schurgers, Felix Manuel Mottaghy, Claudia Goettsch, Willi Jahnen-Dechent
Journal: Theranostics (2023)

Rationale: Calcium plays an essential role in the biology of vertebrates.Calcium content in body fluids is maintained within a narrow physiologic range by feedback control.Phosphate is equally important for metabolism and is likewise controlled, albeit over a wider range.This results in a nearly supersaturated state of calcium phosphate in body liquids driving mineral precipitation in soft tissues, which is actively prevented by calcification inhibitors.The hepatic plasma protein fetuin-A is a circulating mineralization inhibitor regulating calcium phosphate crystal growth and calcified matrix metabolism.Ectopic mineralization is associated with many pathological conditions aggravating their outcome.Current diagnostic methods lack sensitivity towards microcalcifications representing the initial stages of the process.Given the irreversibility of established calcifications, novel diagnostic tools capable of detecting nascent calcium phosphate deposits are highly desirable.Methods: We designed fluorescent fusion proteins consisting of fetuin-A coupled to a green or red fluorescent protein derivate, mEmerald or mRuby3, respectively.The proteins were expressed in mammalian cell lines.Sequence optimization resolved folding issues and increased sensitivity of mineral binding.Chimeric proteins were tested for their ability to detect calcifications in cell cultures and tissue sections retrieved from calcification-prone mice.Results: We employed novel genetically labeled fetuin-A-based fluorescent proteins for the detection of ectopic calcifications.We show that fetuin-A-based imaging agents are non-toxic and suitable for live imaging of microcalcifications beyond the detection limit of conventional staining techniques.The ability of fetuin-A to preferentially bind nascent calcium phosphate crystals allowed the resolution of histopathological detail of early kidney damage that went previously undetected.Endogenous expression of fetuin-A fluorescent fusion proteins allowed extended live imaging of calcifying cells with unprecedented sensitivity and specificity.Conclusion: Ectopic microcalcifications represent a major clinical concern lacking effective diagnostic and treatment options.In this paper, we describe novel highly sensitive fetuin-A-based fluorescent probes for imaging microcalcifications.We show that fusion proteins consisting of a fetuin-A mineral binding moiety and a fluorescent protein are superior to the routine methods for detecting calcifications.They also surpass in continuous live cell imaging the chemically fluorescence labeled fetuin-A, which we established previously.
Interventions Associated With Racial and Ethnic Diversity in US Graduate Medical Education
Authors: Russyan Mark Mabeza, Briana Christophers, Sophia A. Ederaine, Emily J. Glenn, Zachary P. Benton-Slocum, Jasmine R. Marcelin
Journal: JAMA Network Open (2023)

Importance Racially and ethnically minoritized individuals remain underrepresented in graduate medical education relative to their proportion in the population. While many programs and initiatives have been developed to address this problem, there is little consensus regarding strategies that work to improve representation across specialties. Objective To examine and synthesize evidence-based practices that have been used to increase the proportions of underrepresented in medicine (URiM) trainees at US residency and fellowship programs. Evidence Review The authors searched PubMed, Google Scholar, Embase, PsycInfo, ERIC, Cochrane Reviews, Cochrane Trials, CINAHL, Scopus, and PROSPERO electronic databases to identify relevant studies published through January 2022. They screened all titles and abstracts for relevance and read full-text articles to identify articles reporting reliable data describing the outcomes of interventions to improve racial and ethnic diversity among trainees. Findings Twenty-seven articles were included in this review. Two studies reported on fellowship programs. The most common interventions included holistic review (48%), decreased emphasis on United States Medical Licensing Examination Step 1 scores (48%), and explicit institutional messaging regarding the importance of diversity (37%). A combination of interventions was associated with an increased number of URiM applicants, interviewees, and matriculants across various medical and surgical specialties. Conclusions and Relevance In this scoping review, approaches and interventions associated with increased diversity in residency and fellowship programs were identified. Continued efforts are necessary to sustain such efforts and assess long-term outcomes.
Breast Cancer Screening Among Women With Intellectual Disability in Denmark
Authors: Trine Allerslev Horsbøl, Susan Ishøy Michelsen, Tina Harmer Lassen, Knud Juel, Janne Bigaard, Christina Engel Hoei-Hansen, Ilse Vejborg, Lau Caspar Thygesen
Journal: JAMA Network Open (2023)

Importance Breast cancer–specific mortality is increased among women with intellectual disability (ID), and knowledge about participation in breast cancer screening in this group is needed. Objective To examine participation in the Danish national breast cancer screening program among women with ID compared with women without ID. Design, Setting, and Participants This dynamic population-based cohort study assessed participation in the Danish national breast cancer screening program initiated in 2007, targeting women aged 50 to 69 years with a screening interval of 2 years. In all, 6357 women with ID born between 1941 and 1967 and eligible for the screening program were identified in national registers. Women entered the study between January 1, 2007, and December 31, 2017. Subsequently, 273 women were excluded due to a history of carcinoma in situ or breast cancer, and 489 due to registration errors in registers. Each woman was individually age-matched with 10 women without ID (reference group). All women were followed up until March 31, 2021, or censoring (due to death, carcinoma in situ, or breast cancer). Data were analyzed from December 1, 2021, to June 31, 2022. Exposures Intellectual disability was defined as being registered with an ID diagnosis or a diagnosis most likely leading to ID or residing at an institution for persons with ID. Main Outcomes and Measures Participation in breast cancer screening (fully, partly, and never). Results A total of 5595 women with ID and 49 423 age-matched women in the reference group were included in the analysis. Of these, 2747 women with ID (49%) and 24 723 in the reference group (50%) were 50 years of age at study entry; for those older than 50 years, the median age was 51 years (IQR, 50-58 years) in both groups. In all, 1425 women with ID (25%) were fully screened according to guidelines for the Danish breast cancer screening program compared with 30 480 women in the reference group (62%). Women with ID had nearly 5 times higher odds of never being screened compared with the reference group (odds ratio, 4.90 [95% CI, 4.60-5.22]). In all, 2498 women with ID (45%) and 6573 in the reference group (13%) were never screened. The proportion of never-screened women increased with severity of ID, from 834 of 2287 (36%) among women with mild ID to 173 of 212 (82%) among women with profound ID. Conclusions and Relevance The findings of this cohort study suggest that women with ID are markedly less likely to participate in breast cancer screening compared with women without ID. These findings further suggest a need for tailored guidelines and approaches for breast cancer screening in this group of women.
Tumor polyamines as guest cues attract host-functionalized liposomes for targeting and hunting via a bio-orthogonal supramolecular strategy
Authors: Qian Cheng, Zhiqing Yang, Xingping Quan, Yuanfu Ding, Junyan Li, Ziyi Wang, Yonghua Zhao, Xiaoyuan Chen, Ruibing Wang
Journal: Theranostics (2023)

Inspired by the attractions of fruit flies to polyamines of rotten food, we developed a facile, bio-orthogonal, supramolecular homing and hunting strategy, relying on the elevated levels of polyamines in tumor as the natural guest cues to attract cucurbit [7] uril (CB[7]) functionalized liposomes to the tumor site, owing to the strong, bio-orthogonal host-guest interactions between CB[7] and polyamines.This supramolecular homing enabled a high targeting efficiency of CB[7] functionalized liposomes, and allowed better tissue penetration and retention in breast tumor.The employment of a receptor functionalized nanomedicine for direct tropism towards endogenous biomarkers as guest cues, reminiscent of natural chemotaxis but in a bio-orthogonal manner, has not been previously reported, offering new sights to the design and development of new nanoformulations that rely on bio-orthogonal interactions for chemotaxis-guided targeting.
Manufacturer Revenue on Inhalers After Expiration of Primary Patents, 2000-2021
Authors: William B. Feldman, S. Sean Tu, Rasha Alhiary, Aaron S. Kesselheim, Olivier J. Wouters
Journal: JAMA (2023)

This study quantifies the revenue earned on all brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 and compared earnings before and after expiration of primary patents on these products.